A Phase 3 Study to Evaluate the Efficacy of Lifitegrast in Subjects With Dry Eye
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the safety and efficacy of lifitegrast ophthalmic solution compared to placebo in the treatment of dry eye.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Lifitegrast Lifitegrast Ophthalmic Solution (5.0%) |
Drug: Lifitegrast
Lifitegrast Ophthalmic Solution 5.0%
Other Names:
|
Placebo Comparator: Placebo
|
Drug: Placebo
Placebo for Lifitegrast Ophthalmic Solution 5.0%
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 [Baseline to Day 84]
Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.
- Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 [Baseline to Day 84]
Eye dryness score was assessed on a visual analogue scale (a 7-item [burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing and able to read, sign and date the informed consent and HIPAA documents
-
Willing and able to comply with all study procedures
-
Be at least 18 years of age
-
Patient-reported history of dry eye in both eyes
-
A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period
-
Artificial tear use within the past 30 days
Exclusion Criteria:
-
Any ocular condition that, in the opinion of the Investigator, could affect study parameters including, but not limited to, active ocular infection, ocular inflammation, glaucoma, and/or diabetic retinopathy
-
Unwilling to avoid wearing contact lenses for 7 days prior to first visit and for the duration of the study
-
Any blood donation or significant loss of blood within 56 days of Visit 1
-
Any history of immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant.
-
Use of any prohibited medications at any time during the study unless otherwise specified
-
Any significant illness that could interfere with study parameters
-
History of laser assisted in situ keratomileusis (LASIK) or similar type of corneal refractive surgery within 12 months prior to first visit, and/or any other ocular surgical procedure within 12 months prior to first visit; or any scheduled ocular surgical procedure during the study period.
-
Known history of alcohol and/or drug abuse
-
Subjects with Dry eye secondary to scarring or destruction of conjunctival goblet cells (as with Vitamin A deficiency)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | OPUS-2 Investigational Site | Artesia | California | United States | 90701 |
2 | OPUS-2 Investigational Site | Hemet | California | United States | 92545 |
3 | OPUS-2 Investigational Site | Lancaster | California | United States | 93534 |
4 | OPUS-2 Investigational Site | Mission Hills | California | United States | 91345 |
5 | OPUS-2 Investigational Site | Montebello | California | United States | 90640 |
6 | OPUS-2 Investigational Site | Newport Beach | California | United States | 92663 |
7 | OPUS-2 Investigational Site | Petaluma | California | United States | 94954 |
8 | OPUS-2 Investigational SIte | Rancho Cordova | California | United States | 95670 |
9 | OPUS-2 Investigational Site | Danbury | Connecticut | United States | 06810 |
10 | OPUS-2 Investigational Site | Fort Myers | Florida | United States | 33901 |
11 | OPUS-2 Investigational Site | Hoffman Estates | Illinois | United States | 60169 |
12 | OPUS-2 Investigational Site | Indianapolis | Indiana | United States | 46260 |
13 | OPUS-2 Investigational Site | New Albany | Indiana | United States | 47150 |
14 | OPUS-2 Investigational Site | Lexington | Kentucky | United States | 40509 |
15 | OPUS-2 Investigational Site | Saint Paul | Minnesota | United States | 55082 |
16 | OPUS-2 Investigational Site | Chesterfield | Missouri | United States | 63017 |
17 | OPUS-2 Investigational Site | Des Peres | Missouri | United States | 63131 |
18 | OPUS-2 Investigational Site | Independence | Missouri | United States | 64055 |
19 | OPUS-2 Investigational Site | Kansas City | Missouri | United States | 64111 |
20 | OPUS-2 Investigational Site | Washington | Missouri | United States | 63090 |
21 | OPUS-2 Investigational Site | New York | New York | United States | 10016 |
22 | OPUS-2 Investigational Site | New York | New York | United States | 10036 |
23 | OPUS-2 Investigational Site | Wantagh | New York | United States | 11793 |
24 | OPUS-2 Investigational Site | Cleveland | Ohio | United States | 44115 |
25 | OPUS-2 Investigational Site | Philadelphia | Pennsylvania | United States | 19148 |
26 | OPUS-2 Investigational Site | Houston | Texas | United States | 77034 |
27 | OPUS-2 Investigational Site | Houston | Texas | United States | 77055 |
28 | OPUS-2 Investigational Site | League City | Texas | United States | 77573 |
29 | OPUS-2 Investigational Site | San Antonio | Texas | United States | 78209 |
30 | OPUS-2 Investigational Site | San Antonio | Texas | United States | 78229 |
31 | OPUS-2 Investigational Site | Norfolk | Virginia | United States | 23502 |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1118-DRY-300
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Two of 720 participants were excluded from data analysis due to duplication. Therefore, 718 participants were randomized and treated. One participant from placebo arm (N=360) has taken study drug by mistake and considered for "Lifitegrast" arm (N=358). Therefore, Placebo (N=359), Lifitegrast (N=359) were considered for safety analysis. |
Arm/Group Title | Lifitegrast | Placebo |
---|---|---|
Arm/Group Description | ||
Period Title: Overall Study | ||
STARTED | 358 | 360 |
COMPLETED | 321 | 348 |
NOT COMPLETED | 37 | 12 |
Baseline Characteristics
Arm/Group Title | Lifitegrast | Placebo | Total |
---|---|---|---|
Arm/Group Description | Total of all reporting groups | ||
Overall Participants | 358 | 360 | 718 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
58.7
(13.93)
|
58.9
(14.26)
|
58.8
(14.09)
|
Sex: Female, Male (Count of Participants) | |||
Female |
285
79.6%
|
265
73.6%
|
550
76.6%
|
Male |
73
20.4%
|
95
26.4%
|
168
23.4%
|
Outcome Measures
Title | Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 |
---|---|
Description | Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline. |
Time Frame | Baseline to Day 84 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) set included all randomized participants who received at least 1 dose of study drug. |
Arm/Group Title | Lifitegrast | Placebo |
---|---|---|
Arm/Group Description | ||
Measure Participants | 358 | 360 |
Baseline |
2.39
(0.763)
|
2.40
(0.722)
|
Change from Baseline to Day 84 |
-0.73
(0.926)
|
-0.71
(0.943)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Lifitegrast, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.6186 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Effect |
Estimated Value | 0.03 | |
Confidence Interval |
(2-Sided) 95% -0.10 to 0.17 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 |
---|---|
Description | Eye dryness score was assessed on a visual analogue scale (a 7-item [burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome. |
Time Frame | Baseline to Day 84 |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with last observation carried forward (LOCF). |
Arm/Group Title | Lifitegrast | Placebo |
---|---|---|
Arm/Group Description | ||
Measure Participants | 358 | 360 |
Baseline |
69.68
(16.954)
|
69.22
(16.761)
|
Change from Baseline to Day 84 |
-35.30
(28.400)
|
-22.75
(28.600)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Lifitegrast, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Effect |
Estimated Value | 12.61 | |
Confidence Interval |
(2-Sided) 95% 8.51 to 16.70 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | One participant from placebo group (N=360) has taken study drug by mistake and considered for "Lifitegrast" group (N=358). Therefore, Placebo (N)= 359, Lifitegrast (N)=359 were considered for safety analysis. | |||
Arm/Group Title | Lifitegrast | Placebo | ||
Arm/Group Description | ||||
All Cause Mortality |
||||
Lifitegrast | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Lifitegrast | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/359 (0.8%) | 4/359 (1.1%) | ||
Ear and labyrinth disorders | ||||
Vertigo | 1/359 (0.3%) | 1 | 0/359 (0%) | 0 |
Endocrine disorders | ||||
Thyrotoxic crisis | 1/359 (0.3%) | 1 | 0/359 (0%) | 0 |
Gastrointestinal disorders | ||||
Colitis ischaemic | 0/359 (0%) | 0 | 1/359 (0.3%) | 1 |
Musculoskeletal and connective tissue disorders | ||||
Osteoarthritis | 0/359 (0%) | 0 | 1/359 (0.3%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Bladder cancer | 0/359 (0%) | 0 | 1/359 (0.3%) | 1 |
Renal cancer | 1/359 (0.3%) | 1 | 0/359 (0%) | 0 |
Nervous system disorders | ||||
Cerebrovascular accident | 0/359 (0%) | 0 | 1/359 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Lifitegrast | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 102/359 (28.4%) | 30/359 (8.4%) | ||
Eye disorders | ||||
Visual acuity reduced | 18/359 (5%) | 23 | 23/359 (6.4%) | 28 |
General disorders | ||||
Instillation site irritation | 28/359 (7.8%) | 29 | 5/359 (1.4%) | 5 |
Instillation site reaction | 25/359 (7%) | 29 | 4/359 (1.1%) | 4 |
Nervous system disorders | ||||
Dysgeusia | 58/359 (16.2%) | 58 | 1/359 (0.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If a multicentre publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicentre Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Shire (Note: Lifitegrast was divested to Novartis in 2019) |
Phone | +1 866 842 5335 |
ClinicalTransparency@shire.com |
- 1118-DRY-300